Function of reduced-size liver transplant in the rat.

We have studied the function of partial orthotopic liver transplantation in the rat by evaluating prothrombin time (PT), liver blood flow, basal and glucose-stimulated insulin secretion and glucose tolerance, and the reticuloendothelial function (RES) in hepatectomized rats subjected to partial liver transplantation. A graft corresponding to 68% of a normal liver was transplanted to totally hepatectomized rats. Comparison was made between control rats and rats subjected to 32% liver resection. PT was not significantly different in the transplanted group compared with liver-resected and control rats. Laser Doppler flowmetry showed that at 28 days after surgery, blood flow had increased in the transplanted livers. Furthermore, on the third day after transplantation, basal plasma insulin was increased and the plasma insulin response to glucose was exaggerated, suggesting reduced insulin action and impaired insulin degradation. Finally, uptake of radioactive-labeled E. coli bacteria, as a measure of RES function, was not compromised in transplanted animals. Based on these results, we conclude that reduced-size liver transplant in out-bred rats results in fast normalization of liver function after surgery although, immediately after surgery, glucose intolerance is seen.

Impact of arterialization on hepatic oxygen supply, tissue energy phosphates, and outcome after liver transplantation in the rat.

The importance of arterial reconstruction in experimental orthotopic rat liver transplantation is widely acknowledged in the literature. Non-rearterialization of the graft leads to impaired microcirculation and, in chronic models, to severe hepatobiliary damage, together with bile duct proliferation and fibrosis in such livers. The aim of the current study was to investigate the impact of rearterialization on hepatic oxygen tension (pO2), hepatic tissue content of adenine nucleotides, early graft function, and postoperative outcome. Orthotopic liver transplantation was performed in 27 male inbred rats. Ten rats underwent rearterialization and while 17 did not. A group of sham-operated animals (n = 6) served as controls. After reperfusion, liver grafts without arterial reconstruction showed significantly reduced levels of oxygen tension (mean +/- SD, 3.79 +/- 2.20 vs. 10.03 +/- 2.84 mmHg; P < 0.05) and a clear shift toward lower pO2 values in the pO2 histograms, as compared with arterialized grafts. Without arterialization, the level of liver ATP was 65% of that in sham animals, compared with 84% in arterialized livers. Without arterialization, bile secretion was reduced (0.42 +/- 0.04 vs. 0.71 +/- 0.06 mg/min x g liver; (P < 0.001), and the postoperative course of serum alanine transaminase, bilirubin, and alkaline phosphatase revealed severe hepatobiliary damage. These findings allow us to conclude that graft rearterialization is essential to ensure both an adequate oxygen supply and maintenance of tissue ATP. Arterialization may thus be a necessary part of liver transplantation models in this animal species, and should be considered when designing studies on the biochemical, microcirculatory, and histopathological status of the graft.

Partial orthotopic liver transplantation in rats.

A partial orthotopic liver transplantation technique (70% POLT) for use in rats and comparable with the corresponding recipient operation in the 'splitting transplantation' in man was developed. Body weight, liver function, histological and electron-microscopic findings were studied in comparison with whole rat liver transplantation with rearterialization, 30% POLT and corresponding liver resections. After 70 and 30% POLT typical signs of hepatic regeneration were found, but no pathological alterations in the electron-microscopic picture. This POLT model might be helpful for the investigation of unresolved questions in 'splitting transplantation'.

Liver regeneration following 68% partial orthotopic liver transplantation in the rat.

Liver regeneration following transplantation in 'small for size' conditions is not fully understood. We therefore evaluated the regenerative response of transplanted partial liver grafts in outbred rats without the use of immunosuppression and compared it to liver regeneration following resection. The transplanted livers showed enhanced regeneration compared to controls. We suggest that this is caused by activation of the immune system.